Our plans for this Center for the Neuroscience of Mental disorders (CNMD) with a focus on schizophrenia, represent an extension of the present NIMH-funded Center for Neuroscience and Schizophrenia (CNS). The proposed Center continues to exploit the numerous collaborative interactions that exist within the large community of basic and clinical neuroscientists on campus. The general goals of the proposed CNMD are to investigate the involvement of prefrontal cortex in the pathophysiology of schizophrenia by testing the following main hypothesis: Prefrontal cortical dysfunction in schizophrenia is related to a reduction in dopaminergic activity in this region, and to diminished activity in glutamatergic projection neurons. The Center will consist of three cores, one Administrative (Director, E. Stricker), one Clinical (Director, N. Schooler), and the third Statistical (Director, R. Pagano), and four major research programs. Proposed Project 5 (Prefrontal Cortical Regulation of Nucleus Accumbens; Directors, E. Stricker, M. Zigmond) extends research that had been contained in Project 2 of the CNS; its main focus is on the influence of glutamatergic corticofugal fibers on mesolimbic dopamine neurons. Proposed Project 6 (Synapses and their Modulation in the Prefrontal Cortex; Directors, G. Barrionuevo, F. Crepel) is a new project that evolved from Project 1 in the CNS; its main focus is on the relation between structure and function in prefrontal cortical neurons, and the modulatory influence of monoaminergic input on those neurons. Proposed Project 2 (Organization of Primate Prefrontal Cortical Circuitry; Directors, D. Lewis, J. Lund, R. Moore) is a continuation of Project 3 in the CNS; its main focus is on the functional architecture of neuronal circuits in the prefrontal cortex of monkeys and of homologous cortical areas in brains of schizophrenics and normal human controls. Proposed Project 7 (The Role of Prefrontal Cortex in the Cognitive Dysfunctions of Schizophrenia; Directors, J. McClelland, J. Cohen) is another new project; its main goal is to understand the cognitive functions subserved by prefrontal cortex in humans, and their impairment in schizophrenia.